CA2988306A1 - Triazoles pour le traitement de maladies liees a la demyelinisation - Google Patents
Triazoles pour le traitement de maladies liees a la demyelinisation Download PDFInfo
- Publication number
- CA2988306A1 CA2988306A1 CA2988306A CA2988306A CA2988306A1 CA 2988306 A1 CA2988306 A1 CA 2988306A1 CA 2988306 A CA2988306 A CA 2988306A CA 2988306 A CA2988306 A CA 2988306A CA 2988306 A1 CA2988306 A1 CA 2988306A1
- Authority
- CA
- Canada
- Prior art keywords
- 4alkyl
- 6alkylene
- 4alkylene
- independently selected
- 4haloalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000016192 Demyelinating disease Diseases 0.000 title claims abstract description 47
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 150000003852 triazoles Chemical class 0.000 title claims description 4
- -1 triazole compounds Chemical class 0.000 claims abstract description 616
- 150000001875 compounds Chemical class 0.000 claims abstract description 445
- 150000003839 salts Chemical class 0.000 claims abstract description 119
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 57
- 238000000034 method Methods 0.000 claims abstract description 50
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 11
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 505
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 288
- 229910052736 halogen Inorganic materials 0.000 claims description 235
- 150000002367 halogens Chemical class 0.000 claims description 235
- 125000001424 substituent group Chemical group 0.000 claims description 209
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 173
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 165
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 163
- 229910052757 nitrogen Inorganic materials 0.000 claims description 133
- 125000004043 oxo group Chemical group O=* 0.000 claims description 132
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 128
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 99
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 92
- 125000005842 heteroatom Chemical group 0.000 claims description 91
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 91
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 86
- 229910052760 oxygen Inorganic materials 0.000 claims description 86
- 239000001301 oxygen Substances 0.000 claims description 86
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 85
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 84
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 65
- 229910052717 sulfur Chemical group 0.000 claims description 64
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 51
- 239000011593 sulfur Chemical group 0.000 claims description 51
- 201000010099 disease Diseases 0.000 claims description 48
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 125000006413 ring segment Chemical group 0.000 claims description 44
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 43
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 41
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 40
- 208000035475 disorder Diseases 0.000 claims description 38
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 32
- 125000004429 atom Chemical group 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 26
- 125000002950 monocyclic group Chemical group 0.000 claims description 26
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 23
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 22
- 206010012305 Demyelination Diseases 0.000 claims description 21
- 125000004193 piperazinyl group Chemical group 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 230000001737 promoting effect Effects 0.000 claims description 20
- 208000036546 leukodystrophy Diseases 0.000 claims description 19
- 125000003566 oxetanyl group Chemical group 0.000 claims description 19
- 208000007542 Paresis Diseases 0.000 claims description 18
- 210000003050 axon Anatomy 0.000 claims description 18
- 206010069350 Osmotic demyelination syndrome Diseases 0.000 claims description 17
- 125000002393 azetidinyl group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 208000004296 neuralgia Diseases 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 15
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 208000024891 symptom Diseases 0.000 claims description 15
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 15
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 15
- 208000034800 Leukoencephalopathies Diseases 0.000 claims description 14
- 210000004027 cell Anatomy 0.000 claims description 14
- 208000028389 Nerve injury Diseases 0.000 claims description 13
- 208000003435 Optic Neuritis Diseases 0.000 claims description 13
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 230000008764 nerve damage Effects 0.000 claims description 13
- 208000011580 syndromic disease Diseases 0.000 claims description 13
- 208000007101 Muscle Cramp Diseases 0.000 claims description 12
- 208000009885 central pontine myelinolysis Diseases 0.000 claims description 12
- 230000006735 deficit Effects 0.000 claims description 12
- 206010003591 Ataxia Diseases 0.000 claims description 11
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 11
- 208000012902 Nervous system disease Diseases 0.000 claims description 11
- 125000003725 azepanyl group Chemical group 0.000 claims description 11
- 208000018198 spasticity Diseases 0.000 claims description 11
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 11
- 230000004069 differentiation Effects 0.000 claims description 10
- 210000000535 oligodendrocyte precursor cell Anatomy 0.000 claims description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 9
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 8
- 230000004304 visual acuity Effects 0.000 claims description 8
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 7
- 208000011403 Alexander disease Diseases 0.000 claims description 7
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 claims description 7
- 206010021143 Hypoxia Diseases 0.000 claims description 7
- 208000028226 Krabbe disease Diseases 0.000 claims description 7
- 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 claims description 7
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 7
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 claims description 7
- 206010073696 Wallerian degeneration Diseases 0.000 claims description 7
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 7
- 208000008795 neuromyelitis optica Diseases 0.000 claims description 7
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 7
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 claims description 7
- 208000020431 spinal cord injury Diseases 0.000 claims description 7
- 125000002053 thietanyl group Chemical group 0.000 claims description 7
- 208000009174 transverse myelitis Diseases 0.000 claims description 7
- 230000008734 wallerian degeneration Effects 0.000 claims description 7
- 208000032194 Acute haemorrhagic leukoencephalitis Diseases 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 206010002091 Anaesthesia Diseases 0.000 claims description 6
- 208000001827 Ataxia with vitamin E deficiency Diseases 0.000 claims description 6
- 208000006373 Bell palsy Diseases 0.000 claims description 6
- 206010010356 Congenital anomaly Diseases 0.000 claims description 6
- 208000003164 Diplopia Diseases 0.000 claims description 6
- 241000045500 Diseae Species 0.000 claims description 6
- 206010013887 Dysarthria Diseases 0.000 claims description 6
- 206010017577 Gait disturbance Diseases 0.000 claims description 6
- 208000015872 Gaucher disease Diseases 0.000 claims description 6
- 206010019468 Hemiplegia Diseases 0.000 claims description 6
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 6
- 206010021036 Hyponatraemia Diseases 0.000 claims description 6
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 6
- 201000003533 Leber congenital amaurosis Diseases 0.000 claims description 6
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 claims description 6
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims description 6
- 206010027925 Monoparesis Diseases 0.000 claims description 6
- 206010061296 Motor dysfunction Diseases 0.000 claims description 6
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 6
- 206010028289 Muscle atrophy Diseases 0.000 claims description 6
- 206010028570 Myelopathy Diseases 0.000 claims description 6
- 208000002033 Myoclonus Diseases 0.000 claims description 6
- 206010063534 Ocular dysmetria Diseases 0.000 claims description 6
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 6
- 206010033799 Paralysis Diseases 0.000 claims description 6
- 206010033885 Paraparesis Diseases 0.000 claims description 6
- 206010033892 Paraplegia Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 206010034701 Peroneal nerve palsy Diseases 0.000 claims description 6
- 206010067063 Progressive relapsing multiple sclerosis Diseases 0.000 claims description 6
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 6
- 208000005392 Spasm Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 6
- 206010044696 Tropical spastic paresis Diseases 0.000 claims description 6
- 208000036826 VIIth nerve paralysis Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 230000037005 anaesthesia Effects 0.000 claims description 6
- 238000001949 anaesthesia Methods 0.000 claims description 6
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 230000004064 dysfunction Effects 0.000 claims description 6
- 201000002491 encephalomyelitis Diseases 0.000 claims description 6
- 201000006517 essential tremor Diseases 0.000 claims description 6
- 201000003264 familial isolated deficiency of vitamin E Diseases 0.000 claims description 6
- 206010019465 hemiparesis Diseases 0.000 claims description 6
- 230000001146 hypoxic effect Effects 0.000 claims description 6
- 230000000302 ischemic effect Effects 0.000 claims description 6
- 201000010901 lateral sclerosis Diseases 0.000 claims description 6
- 230000033001 locomotion Effects 0.000 claims description 6
- 208000005264 motor neuron disease Diseases 0.000 claims description 6
- 230000020763 muscle atrophy Effects 0.000 claims description 6
- 201000000585 muscular atrophy Diseases 0.000 claims description 6
- 230000002981 neuropathic effect Effects 0.000 claims description 6
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 201000001119 neuropathy Diseases 0.000 claims description 6
- 230000007823 neuropathy Effects 0.000 claims description 6
- 206010029864 nystagmus Diseases 0.000 claims description 6
- 206010030875 ophthalmoplegia Diseases 0.000 claims description 6
- 230000003204 osmotic effect Effects 0.000 claims description 6
- 208000021090 palsy Diseases 0.000 claims description 6
- 208000035824 paresthesia Diseases 0.000 claims description 6
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
- 230000011514 reflex Effects 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 230000009529 traumatic brain injury Effects 0.000 claims description 6
- 201000006397 traumatic glaucoma Diseases 0.000 claims description 6
- 208000006961 tropical spastic paraparesis Diseases 0.000 claims description 6
- 208000002670 vitamin B12 deficiency Diseases 0.000 claims description 6
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 5
- 206010008072 Cerebellar syndrome Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
- 206010009346 Clonus Diseases 0.000 claims description 5
- 208000014094 Dystonic disease Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 208000015178 Hurler syndrome Diseases 0.000 claims description 5
- 206010022520 Intention tremor Diseases 0.000 claims description 5
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims description 5
- 208000014060 Niemann-Pick disease Diseases 0.000 claims description 5
- 206010034962 Photopsia Diseases 0.000 claims description 5
- 208000019155 Radiation injury Diseases 0.000 claims description 5
- 206010044565 Tremor Diseases 0.000 claims description 5
- 208000012886 Vertigo Diseases 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 208000010118 dystonia Diseases 0.000 claims description 5
- 229910000065 phosphene Inorganic materials 0.000 claims description 5
- 230000000272 proprioceptive effect Effects 0.000 claims description 5
- 208000022749 pupil disease Diseases 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 231100000889 vertigo Toxicity 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
- 206010021118 Hypotonia Diseases 0.000 claims description 4
- 208000007379 Muscle Hypotonia Diseases 0.000 claims description 4
- 206010037714 Quadriplegia Diseases 0.000 claims description 4
- 201000001881 impotence Diseases 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 206010047385 vestibular ataxia Diseases 0.000 claims description 4
- 201000003892 detrusor sphincter dyssynergia Diseases 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 201000005936 periventricular leukomalacia Diseases 0.000 claims description 2
- DJIVFMFINBXBJO-HBASGXJGSA-N G20 Chemical compound C1=NC(C(NC(N)=N2)=O)=C2N1[C@@H]([C@@H]1O)O[C@H](COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2CO)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)[C@H]1OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=C(NC2=O)N)=C2N=C1 DJIVFMFINBXBJO-HBASGXJGSA-N 0.000 claims 6
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 208000022526 Canavan disease Diseases 0.000 claims 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims 1
- 241000606329 Myzomyia Species 0.000 claims 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- 208000005587 Refsum Disease Diseases 0.000 claims 1
- 206010048215 Xanthomatosis Diseases 0.000 claims 1
- 208000030597 adult Refsum disease Diseases 0.000 claims 1
- 201000001801 internuclear ophthalmoplegia Diseases 0.000 claims 1
- 208000028780 ocular motility disease Diseases 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 abstract description 46
- 239000000203 mixture Substances 0.000 abstract description 40
- 230000003210 demyelinating effect Effects 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 186
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 103
- 229910052805 deuterium Inorganic materials 0.000 description 63
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 63
- 125000003944 tolyl group Chemical group 0.000 description 60
- 150000001975 deuterium Chemical group 0.000 description 59
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 57
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 57
- 150000001412 amines Chemical class 0.000 description 56
- 235000002639 sodium chloride Nutrition 0.000 description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 45
- MPSUGQWRVNRJEE-UHFFFAOYSA-N triazol-1-amine Chemical compound NN1C=CN=N1 MPSUGQWRVNRJEE-UHFFFAOYSA-N 0.000 description 43
- 125000000623 heterocyclic group Chemical group 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 229910052698 phosphorus Inorganic materials 0.000 description 35
- 125000001153 fluoro group Chemical group F* 0.000 description 29
- 125000005936 piperidyl group Chemical group 0.000 description 29
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 28
- WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 26
- 150000004985 diamines Chemical class 0.000 description 24
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 23
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 23
- GHUDJFJZFUVPIQ-UHFFFAOYSA-N 5-phenyl-1h-1,2,4-triazol-3-amine Chemical compound NC1=NNC(C=2C=CC=CC=2)=N1 GHUDJFJZFUVPIQ-UHFFFAOYSA-N 0.000 description 21
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 20
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 20
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 19
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 19
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 17
- 125000000217 alkyl group Chemical group 0.000 description 16
- 229960004979 fampridine Drugs 0.000 description 16
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 15
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 15
- 210000004248 oligodendroglia Anatomy 0.000 description 15
- 102000006386 Myelin Proteins Human genes 0.000 description 14
- 108010083674 Myelin Proteins Proteins 0.000 description 14
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 14
- 210000005012 myelin Anatomy 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 13
- 125000004434 sulfur atom Chemical group 0.000 description 13
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 12
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 10
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- UPZZNNQSHZBTAQ-UHFFFAOYSA-N 1-phenyl-1,2,4-triazol-3-amine Chemical compound N1=C(N)N=CN1C1=CC=CC=C1 UPZZNNQSHZBTAQ-UHFFFAOYSA-N 0.000 description 8
- ZSXQDGMZXKOADT-UHFFFAOYSA-N 2-morpholin-4-ylpyridin-4-amine Chemical compound NC1=CC=NC(N2CCOCC2)=C1 ZSXQDGMZXKOADT-UHFFFAOYSA-N 0.000 description 8
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
- ATAOZKYWWCZHIU-UHFFFAOYSA-N 3-N-(3-morpholin-4-ylcyclobutyl)benzene-1,3-diamine Chemical compound O1CCN(CC1)C1CC(C1)NC=1C=C(C=CC=1)N ATAOZKYWWCZHIU-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000005713 exacerbation Effects 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 238000002595 magnetic resonance imaging Methods 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 230000004783 oxidative metabolism Effects 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- 102220473072 Chemerin-like receptor 2_R14Q_mutation Human genes 0.000 description 5
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 5
- 102220534102 Kelch-like ECH-associated protein 1_R15A_mutation Human genes 0.000 description 5
- 206010028632 Myokymia Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 5
- 206010072731 White matter lesion Diseases 0.000 description 5
- 230000003376 axonal effect Effects 0.000 description 5
- 208000032257 benign familial neonatal 1 seizures Diseases 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 230000023105 myelination Effects 0.000 description 5
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 5
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 102220493465 Sodium/calcium exchanger 3_R12A_mutation Human genes 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 4
- 150000003857 carboxamides Chemical class 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 208000030159 metabolic disease Diseases 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 4
- 230000008439 repair process Effects 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 3
- RAXHQNRHFRYLPS-SSDOTTSWSA-N 2-[(3R)-3-fluoropyrrolidin-1-yl]pyridin-4-amine Chemical compound F[C@H]1CN(CC1)C1=NC=CC(=C1)N RAXHQNRHFRYLPS-SSDOTTSWSA-N 0.000 description 3
- KSUYFCSSOHFITQ-UHFFFAOYSA-N 2-morpholin-4-ylbenzonitrile Chemical compound N#CC1=CC=CC=C1N1CCOCC1 KSUYFCSSOHFITQ-UHFFFAOYSA-N 0.000 description 3
- ATBTTYMDWVIEIT-UHFFFAOYSA-N 3-(3-morpholin-4-ylazetidin-1-yl)pyridin-2-amine Chemical compound O1CCN(CC1)C1CN(C1)C=1C(=NC=CC=1)N ATBTTYMDWVIEIT-UHFFFAOYSA-N 0.000 description 3
- DRKMRCRNAWCBKQ-UHFFFAOYSA-N 3-[4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-amine Chemical compound O1CC(C1)N1CCN(CC1)C=1C(=NC=CC=1)N DRKMRCRNAWCBKQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 3
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 3
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000007844 axonal damage Effects 0.000 description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 208000012268 mitochondrial disease Diseases 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000000626 neurodegenerative effect Effects 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 3
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 229940055764 triaz Drugs 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- 230000001228 trophic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VKZRWSNIWNFCIQ-WDSKDSINSA-N (2s)-2-[2-[[(1s)-1,2-dicarboxyethyl]amino]ethylamino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NCCN[C@H](C(O)=O)CC(O)=O VKZRWSNIWNFCIQ-WDSKDSINSA-N 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 2
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 2
- WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000005983 2,5-diazabicyclo[2.2.1]heptan-2-yl group Chemical group 0.000 description 2
- DOTQVGHNPGOBGZ-UHFFFAOYSA-N 2-(3,6-dihydro-2H-pyran-4-yl)pyridin-4-amine Chemical compound O1CCC(=CC1)C1=NC=CC(=C1)N DOTQVGHNPGOBGZ-UHFFFAOYSA-N 0.000 description 2
- OGGDMYLMXALBMJ-UHFFFAOYSA-N 2-(4-methylpiperidin-1-yl)pyridin-4-amine Chemical compound C1CC(C)CCN1C1=CC(N)=CC=N1 OGGDMYLMXALBMJ-UHFFFAOYSA-N 0.000 description 2
- OWYLWJWVTYHWJP-UHFFFAOYSA-N 2-(oxan-4-yl)pyridin-4-amine Chemical compound NC1=CC=NC(C2CCOCC2)=C1 OWYLWJWVTYHWJP-UHFFFAOYSA-N 0.000 description 2
- RAXHQNRHFRYLPS-ZETCQYMHSA-N 2-[(3S)-3-fluoropyrrolidin-1-yl]pyridin-4-amine Chemical compound F[C@@H]1CN(CC1)C1=NC=CC(=C1)N RAXHQNRHFRYLPS-ZETCQYMHSA-N 0.000 description 2
- AREWBDCXCVYYMJ-UHFFFAOYSA-N 2-[1-(oxetan-3-yl)pyrrolidin-3-yl]benzene-1,3-diamine Chemical compound O1CC(C1)N1CC(CC1)C1=C(C=CC=C1N)N AREWBDCXCVYYMJ-UHFFFAOYSA-N 0.000 description 2
- XTCJYQFQKXYIMZ-UHFFFAOYSA-N 2-piperidin-1-ylpyridin-4-amine Chemical compound NC1=CC=NC(N2CCCCC2)=C1 XTCJYQFQKXYIMZ-UHFFFAOYSA-N 0.000 description 2
- YWOWJQMFMXHLQD-UHFFFAOYSA-N 3-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=CC=C1C(F)(F)F YWOWJQMFMXHLQD-UHFFFAOYSA-N 0.000 description 2
- APSMDEASWYNKSE-UHFFFAOYSA-N 3-n-(oxetan-3-yl)benzene-1,3-diamine Chemical compound NC1=CC=CC(NC2COC2)=C1 APSMDEASWYNKSE-UHFFFAOYSA-N 0.000 description 2
- KFQHVPAQPKJTHF-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-1h-1,2,4-triazol-3-amine Chemical compound NC1=NNC(C=2C=C(C=CC=2)C(F)(F)F)=N1 KFQHVPAQPKJTHF-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 description 2
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 2
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 206010067601 Dysmyelination Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102220581910 RNA N6-adenosine-methyltransferase METTL16_R10A_mutation Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
- QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 206010008129 cerebral palsy Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000007278 cognition impairment Effects 0.000 description 2
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical group OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 125000004431 deuterium atom Chemical group 0.000 description 2
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
- 229940043264 dodecyl sulfate Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 230000005021 gait Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000005283 ground state Effects 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000005445 isotope effect Effects 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 2
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000005070 sphincter Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- PVPTUASRAVWKGX-UHFFFAOYSA-N 1,2-dihydrotriazol-3-amine Chemical compound NN1NNC=C1 PVPTUASRAVWKGX-UHFFFAOYSA-N 0.000 description 1
- 150000000185 1,3-diols Chemical class 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
- FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
- 125000005962 1,4-oxazepanyl group Chemical group 0.000 description 1
- SWKVQJQPSGTEBD-UHFFFAOYSA-N 1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyrazin-3-one Chemical compound C1NCCN2C(=O)OCC21 SWKVQJQPSGTEBD-UHFFFAOYSA-N 0.000 description 1
- NCXUNZWLEYGQAH-UHFFFAOYSA-N 1-(dimethylamino)propan-2-ol Chemical compound CC(O)CN(C)C NCXUNZWLEYGQAH-UHFFFAOYSA-N 0.000 description 1
- 125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- NSRUVKRNGYFSKD-UHFFFAOYSA-N 2-(oxetan-3-yl)benzene-1,3-diamine Chemical compound O1CC(C1)C1=C(C=CC=C1N)N NSRUVKRNGYFSKD-UHFFFAOYSA-N 0.000 description 1
- NSNDANIBKZPHSS-UHFFFAOYSA-N 2-(oxolan-3-yl)benzene-1,3-diamine Chemical compound O1CC(CC1)C1=C(C=CC=C1N)N NSNDANIBKZPHSS-UHFFFAOYSA-N 0.000 description 1
- LUZZMLVLFVZPHN-UHFFFAOYSA-N 2-[(2-methyloxolan-2-yl)methyl]benzene-1,3-diamine Chemical compound CC1(OCCC1)CC1=C(C=CC=C1N)N LUZZMLVLFVZPHN-UHFFFAOYSA-N 0.000 description 1
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- DRLLLIRFDWLLNV-UHFFFAOYSA-N 2-piperazin-1-ylthietane 1,1-dioxide Chemical compound N1(CCNCC1)C1CCS1(=O)=O DRLLLIRFDWLLNV-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZBSQRSAMKYIVHH-UHFFFAOYSA-N 2-pyrrolidin-1-ylpyridin-4-amine Chemical compound NC1=CC=NC(N2CCCC2)=C1 ZBSQRSAMKYIVHH-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- SRQUMADGZOWYEO-UHFFFAOYSA-N 3-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-2-amine Chemical compound N1CCC(=CC1)C=1C(=NC=CC=1)N SRQUMADGZOWYEO-UHFFFAOYSA-N 0.000 description 1
- BOMRADAXQDYILQ-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)pyridin-2-amine Chemical compound C1CN(C)CCN1C1=CC=CN=C1N BOMRADAXQDYILQ-UHFFFAOYSA-N 0.000 description 1
- DVPDWHONZWNAMO-UHFFFAOYSA-N 3-(oxan-3-yloxy)pyridin-2-amine Chemical compound O1CC(CCC1)OC=1C(=NC=CC=1)N DVPDWHONZWNAMO-UHFFFAOYSA-N 0.000 description 1
- BIWPHYJIQLJIML-UHFFFAOYSA-N 3-(oxetan-3-ylmethoxy)pyridin-2-amine Chemical compound O1CC(C1)COC=1C(=NC=CC=1)N BIWPHYJIQLJIML-UHFFFAOYSA-N 0.000 description 1
- SHGFPRYTIRRHOK-UHFFFAOYSA-N 3-N-[(4-methylmorpholin-3-yl)methyl]benzene-1,3-diamine Chemical compound CN1C(COCC1)CNC=1C=C(C=CC=1)N SHGFPRYTIRRHOK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- UXNIQDLZIQFZLI-UHFFFAOYSA-N 3-methoxy-6-[4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-amine Chemical compound COC=1C(=NC(=CC=1)N1CCN(CC1)C1COC1)N UXNIQDLZIQFZLI-UHFFFAOYSA-N 0.000 description 1
- LCQRJTVOHBHAGT-UHFFFAOYSA-N 3-methyl-2-N-(oxolan-3-yl)pyridine-2,6-diamine Chemical compound CC=1C(=NC(=CC=1)N)NC1COCC1 LCQRJTVOHBHAGT-UHFFFAOYSA-N 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JURDUOAJFHIOOQ-UHFFFAOYSA-N 3-morpholin-4-yl-4-(trifluoromethyl)pyridin-2-amine Chemical compound O1CCN(CC1)C=1C(=NC=CC=1C(F)(F)F)N JURDUOAJFHIOOQ-UHFFFAOYSA-N 0.000 description 1
- KSRWGJRHJUQFTH-UHFFFAOYSA-N 3-morpholin-4-ylpyridin-2-amine Chemical compound NC1=NC=CC=C1N1CCOCC1 KSRWGJRHJUQFTH-UHFFFAOYSA-N 0.000 description 1
- AGFILYMCCYWIQY-UHFFFAOYSA-N 3-n-(2-morpholin-4-ylethyl)benzene-1,3-diamine Chemical compound NC1=CC=CC(NCCN2CCOCC2)=C1 AGFILYMCCYWIQY-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- LTEBKKFVDRXZHW-UHFFFAOYSA-N 3-piperazin-1-ylpyridin-2-amine Chemical compound NC1=NC=CC=C1N1CCNCC1 LTEBKKFVDRXZHW-UHFFFAOYSA-N 0.000 description 1
- OSHXXXUMLUVXTJ-UHFFFAOYSA-N 3-piperidin-4-ylpyridin-2-amine Chemical compound NC1=NC=CC=C1C1CCNCC1 OSHXXXUMLUVXTJ-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
- DZAOMPRTHPAMSK-UHFFFAOYSA-N 5-[3-fluoro-5-(3-methoxyazetidin-1-yl)phenyl]-1H-1,2,4-triazol-3-amine Chemical compound FC=1C=C(C=C(C=1)N1CC(C1)OC)C1=NC(=NN1)N DZAOMPRTHPAMSK-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- KPNUOWMETDITOG-UHFFFAOYSA-N 6-n-(oxolan-3-yl)pyridine-2,6-diamine Chemical compound NC1=CC=CC(NC2COCC2)=N1 KPNUOWMETDITOG-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 101000856746 Bos taurus Cytochrome c oxidase subunit 7A1, mitochondrial Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- WRSCCOOXAMHXDJ-UHFFFAOYSA-N CC1(COC1)N1CCN(CC1)C=1C(=NC=CC=1)N Chemical compound CC1(COC1)N1CCN(CC1)C=1C(=NC=CC=1)N WRSCCOOXAMHXDJ-UHFFFAOYSA-N 0.000 description 1
- YRSJDUZFFSRJQD-UHFFFAOYSA-N COCC1=CC(=NC=N1)C1=NC(=NN1)N Chemical compound COCC1=CC(=NC=N1)C1=NC(=NN1)N YRSJDUZFFSRJQD-UHFFFAOYSA-N 0.000 description 1
- 101100511175 Caenorhabditis elegans lim-4 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 101000988966 Escherichia coli Heat-stable enterotoxin A3/A4 Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 241000132446 Inula Species 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101150071228 Lifr gene Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010048393 Multiple sclerosis relapse Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- FUJWMQDBFIUKAA-UHFFFAOYSA-N O1C(CCC1)CCC1=C(C=CC=C1N)N Chemical compound O1C(CCC1)CCC1=C(C=CC=C1N)N FUJWMQDBFIUKAA-UHFFFAOYSA-N 0.000 description 1
- QEJXRGHSLCATBM-UHFFFAOYSA-N O1CCN(CC1)C=1C(=NC=CC=1N)N1CCOCC1 Chemical compound O1CCN(CC1)C=1C(=NC=CC=1N)N1CCOCC1 QEJXRGHSLCATBM-UHFFFAOYSA-N 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical class CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- AXMNGEUJXLXFRY-UHFFFAOYSA-N azaspirodecane Chemical compound C1CCCC21CCNCC2 AXMNGEUJXLXFRY-UHFFFAOYSA-N 0.000 description 1
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 1
- PBIUUJCEMUAWJJ-UHFFFAOYSA-N azetidine-3-carbonitrile Chemical compound N#CC1CNC1 PBIUUJCEMUAWJJ-UHFFFAOYSA-N 0.000 description 1
- VALZSZJVEFACEZ-UHFFFAOYSA-N azetidine-3-carboxamide Chemical compound NC(=O)C1CNC1 VALZSZJVEFACEZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 101150032057 cseA gene Proteins 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- RUYNTLUDGSFPFZ-UHFFFAOYSA-N cyclobutanol Chemical compound OC1[CH]CC1 RUYNTLUDGSFPFZ-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- XRLDSWLMHUQECH-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1CCCC1 XRLDSWLMHUQECH-UHFFFAOYSA-N 0.000 description 1
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005959 diazepanyl group Chemical group 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001856 erectile effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000005969 isothiazolinyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 230000003458 metachromatic effect Effects 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- GDTFIRYHAYIXIP-UHFFFAOYSA-N methoxycyclobutane Chemical compound COC1CCC1 GDTFIRYHAYIXIP-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- UZUQIGYNEIUVNT-UHFFFAOYSA-N n-[4-(furan-2-yl)-1,3-thiazol-2-yl]formamide Chemical compound S1C(NC=O)=NC(C=2OC=CC=2)=C1 UZUQIGYNEIUVNT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
- 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- TWSTVYFPWIGASI-UHFFFAOYSA-N oxetan-3-ol Chemical compound OC1COC1.OC1COC1 TWSTVYFPWIGASI-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- ZGNXATVKGIJQGC-UHFFFAOYSA-N piperidine-3-carbonitrile Chemical compound N#CC1CCCNC1 ZGNXATVKGIJQGC-UHFFFAOYSA-N 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102200160920 rs35304565 Human genes 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000006300 thietan-3-yl group Chemical group [H]C1([H])SC([H])([H])C1([H])* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention concerne des composés de triazole de formule I et I' ou des sels pharmaceutiquement acceptables de ceux-ci, utiles en tant que modulateurs de maladies liées à la démyélinisation. L'invention concerne également des compositions pharmaceutiquement acceptables comprenant lesdits composés, des procédés d'utilisation des compositions et des kits associés dans le traitement de diverses maladies liées à la démyélinisation et neurodégénératives, notamment la sclérose en plaques.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562171784P | 2015-06-05 | 2015-06-05 | |
US62/171,784 | 2015-06-05 | ||
US201662326471P | 2016-04-22 | 2016-04-22 | |
US62/326,471 | 2016-04-22 | ||
PCT/US2016/035847 WO2016197009A1 (fr) | 2015-06-05 | 2016-06-03 | Triazoles pour le traitement de maladies liées à la démyélinisation |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2988306A1 true CA2988306A1 (fr) | 2016-12-08 |
Family
ID=56409675
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2988306A Abandoned CA2988306A1 (fr) | 2015-06-05 | 2016-06-03 | Triazoles pour le traitement de maladies liees a la demyelinisation |
Country Status (8)
Country | Link |
---|---|
US (2) | US10118904B2 (fr) |
EP (1) | EP3302465A1 (fr) |
AU (1) | AU2016270373A1 (fr) |
CA (1) | CA2988306A1 (fr) |
HK (1) | HK1252425A1 (fr) |
TW (1) | TW201708195A (fr) |
UY (1) | UY36713A (fr) |
WO (1) | WO2016197009A1 (fr) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3302465A1 (fr) * | 2015-06-05 | 2018-04-11 | Vertex Pharmaceuticals Incorporated | Triazoles pour le traitement de maladies liées à la démyélinisation |
TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Hdac抑制劑與pd-l1抑制劑之組合治療 |
WO2018106646A1 (fr) * | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Aminotriazoles pour traiter des maladies démyélinisantes |
KR102635936B1 (ko) * | 2016-12-14 | 2024-02-13 | 에스케이바이오팜 주식회사 | 탈수초성 질환의 예방, 경감 또는 치료를 위한 카바메이트 화합물의 용도 |
US20230067929A1 (en) * | 2018-12-17 | 2023-03-02 | Tolremo Therapeutics Ag | Heterocyclic derivatives, pharmaceutical compositions and their use in the treatment, amelioration or prevention of cancer |
JP7451699B2 (ja) | 2019-11-06 | 2024-03-18 | ユハン コーポレーション | ピロリジン及びピペリジン化合物 |
WO2021130723A1 (fr) * | 2019-12-24 | 2021-07-01 | Cadila Healthcare Limited | Nouveaux composés appropriés pour le traitement de la dyslipidémie |
WO2023097230A1 (fr) * | 2021-11-23 | 2023-06-01 | Genentech, Inc. | Modulateurs bicycliques spirocycliques de la biosynthèse du cholestérol et leur utilisation pour favoriser la remyélinisation |
EP4436975A1 (fr) * | 2021-11-23 | 2024-10-02 | Genentech, Inc. | Modulateurs cycliques de type spirocycliques de la biosynthèse du cholestérol et leur utilisation pour favoriser la remyélinisation |
CN114085197B (zh) * | 2021-12-01 | 2024-03-29 | 合肥创新医药技术有限公司 | 4-(3-三氟甲基苯基)-1-哌嗪-乙醇、氟班色林中间体、氟班色林的合成方法 |
WO2024051667A1 (fr) * | 2022-09-05 | 2024-03-14 | 南京正大天晴制药有限公司 | Composé triazole substitué inhibiteur d'axl |
EP4378932A1 (fr) * | 2022-11-30 | 2024-06-05 | Universität Bern | Nouveaux inhibiteurs de cd93 |
Family Cites Families (124)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU688751B2 (en) | 1993-01-12 | 1998-03-19 | Biogen Idec Ma Inc. | Recombinant anti-VLA4 antibody molecules |
DK0682529T4 (da) | 1993-02-09 | 2006-05-15 | Biogen Idec Inc | Antistof til behandling af insulinkrævende diabetes |
US5840299A (en) | 1994-01-25 | 1998-11-24 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule VLA-4 |
US6964945B1 (en) | 1998-09-25 | 2005-11-15 | The Procter & Gamble Company | Solid detergent compositions |
US6596747B2 (en) | 1998-10-29 | 2003-07-22 | Bristol-Myers Squibb Company | Compounds derived from an amine nucleus and pharmaceutical compositions comprising same |
DE60137405D1 (de) | 2000-02-18 | 2009-03-05 | Kyowa Hakko Kirin Co Ltd | Isoxazol- und thiazolverbindungen und ihre verwendung als medikamente |
ES2242771T5 (es) | 2000-09-15 | 2011-10-14 | Vertex Pharmaceuticals Incorporated | Compuestos de pirazol útiles como inhibidores de proteína quinasas. |
US7169818B2 (en) | 2000-10-03 | 2007-01-30 | University Of Virginia Patent Foundation | Lysophosphatidic acid receptor agonists and antagonists |
EP1533294A4 (fr) | 2002-05-28 | 2007-07-04 | Ono Pharmaceutical Co | Derive de beta-alanine et utilisation correspondante |
EP1553075B1 (fr) | 2002-10-03 | 2013-08-14 | Ono Pharmaceutical Co., Ltd. | Antagonistes des recepteurs de l'acide lysophosphatidique (lpa) |
EP2248899B8 (fr) | 2003-03-19 | 2015-07-15 | Biogen MA Inc. | Protéine de liaison du récepteur NOGO |
WO2005012269A1 (fr) | 2003-08-05 | 2005-02-10 | Ajinomoto Co., Inc. | Nouveau compose azole |
JP4889489B2 (ja) | 2003-08-06 | 2012-03-07 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼのインヒビターとして有用なアミノトリアゾール化合物 |
EP1776136B1 (fr) | 2004-06-24 | 2012-10-03 | Biogen Idec MA Inc. | Traitement d'etats pathologiques impliquant la demyelinisation |
WO2006017673A2 (fr) | 2004-08-03 | 2006-02-16 | Biogen Idec Ma Inc. | Influence du taj sur les fonctions neuronales |
PT1811998E (pt) | 2004-10-21 | 2010-12-23 | Vertex Pharma | Triazóis úteis como inibidores de proteína quinases |
EP2238986A3 (fr) | 2005-07-08 | 2010-11-03 | Biogen Idec MA Inc. | Anticorps Sp35 et utilisations associées |
EP1940446A4 (fr) | 2005-08-25 | 2009-08-05 | Biogen Idec Inc | Polypeptides et fragments polypeptidiques du recepteur nogo et leurs utilisations |
WO2007056163A2 (fr) | 2005-11-03 | 2007-05-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines utiles en tant qu'inhibiteurs de kinases |
CA2628451A1 (fr) | 2005-11-04 | 2007-05-18 | Biogen Idec Ma Inc. | Procedes favorisant la croissance des neurites et la survie des neurones dopaminergiques |
AU2006315334B2 (en) | 2005-11-16 | 2011-05-19 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
NZ569428A (en) | 2005-12-02 | 2012-11-30 | Biogen Idec Inc | Treatment of conditions involving demyelination with a Sp35 antagonist |
WO2007098283A2 (fr) | 2006-02-27 | 2007-08-30 | Biogen Idec Ma Inc. | Utilisation d'antagonistes de molécules complexes du récepteur maif (macrophage migration-inhibitory factors) et de facteurs neurotrophiques pour traiter des maladies et des troubles neurologiques |
EP2023735A4 (fr) | 2006-05-15 | 2011-05-25 | Biogen Idec Inc | UTILISATION D'ANTAGONISTES DU RÉCEPTEUR Nogo 1 (NgR1) POUR FAVORISER LA SURVIE DES OLIGODENDROCYTES |
WO2008013782A2 (fr) | 2006-07-24 | 2008-01-31 | Biogen Idec Ma Inc. | Procédés pour favoriser la myélinisation, la survie neuronale et la différenciation des oligodendrocytes par administration d'antagonistes de sp35 ou trka |
WO2008014286A1 (fr) | 2006-07-24 | 2008-01-31 | University Of Virginia Patent Foundation | Antagonistes du récepteur vinyle phosphonate acide lysophosphatidique |
WO2008057940A1 (fr) | 2006-11-02 | 2008-05-15 | Vertex Pharmaceuticals Incorporated | Aminopyridines et aminopyrimidines utiles en tant qu'inhibiteurs de protéines kinases |
EP1921073A1 (fr) | 2006-11-10 | 2008-05-14 | Laboratorios del Dr. Esteve S.A. | 1,2,4-Triazoles en tant qu'inhibiteurs du récepteur sigma |
JP2010513567A (ja) | 2006-12-19 | 2010-04-30 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼの阻害剤として有用なアミノピリミジン |
WO2008083356A1 (fr) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Triazoles substitués utilisés comme inhibiteurs d'axl |
EP2068887B1 (fr) | 2007-01-09 | 2014-03-12 | Biogen Idec MA Inc. | Anticorps sp35 et leurs utilisations |
NZ580884A (en) | 2007-05-02 | 2012-02-24 | Vertex Pharma | Thiazoles and pyrazoles useful as kinase inhibitors |
CN101687852A (zh) | 2007-05-24 | 2010-03-31 | 沃泰克斯药物股份有限公司 | 可用作激酶抑制剂的噻唑类和吡唑类化合物 |
WO2009023854A1 (fr) | 2007-08-15 | 2009-02-19 | University Of Virginia Patent Foundation | Analogues bicycliques de 1-phosphate de sphingosine |
CN101842109B (zh) | 2007-09-05 | 2014-01-29 | 诺沃-诺迪斯克有限公司 | 用a-b-c-d-衍生的肽和它们的治疗用途 |
DE102007047735A1 (de) | 2007-10-05 | 2009-04-09 | Merck Patent Gmbh | Thiazolderivate |
DE102007047737A1 (de) | 2007-10-05 | 2009-04-30 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
DE102007047738A1 (de) | 2007-10-05 | 2009-04-09 | Merck Patent Gmbh | Imidazolderivate |
AU2008311251B9 (en) | 2007-10-11 | 2014-04-17 | Biogen Ma Inc. | Methods for treating pressure induced optic neuropathy, preventing neuronal degeneration and promoting neuronal cell, survival via administration of lingo-1 antagonists and TrkB agonists |
JP5754046B2 (ja) | 2007-11-08 | 2015-07-22 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | 脱髄を伴う状態の治療におけるlingo−4アンタゴニストの使用 |
JP2011513483A (ja) | 2008-03-10 | 2011-04-28 | バーテックス ファーマシューティカルズ インコーポレイテッド | タンパク質キナーゼの阻害剤として有用なピリミジンおよびピリジン |
ES2637805T3 (es) | 2008-05-05 | 2017-10-17 | Sanofi | Derivados de ácido ciclopentanocarboxílico fusionados sustituidos por acilamino y su uso como productos farmacéuticos |
US8058406B2 (en) | 2008-07-09 | 2011-11-15 | Biogen Idec Ma Inc. | Composition comprising antibodies to LINGO or fragments thereof |
JP2011198778A (ja) | 2008-07-15 | 2011-10-06 | Panasonic Corp | 熱発電デバイスの製造方法 |
ES2613739T3 (es) | 2008-10-30 | 2017-05-25 | Biogen Ma Inc. | Análogos heterobicíclicos de 1-fosfato de esfingosina |
ES2466695T3 (es) | 2008-10-30 | 2014-06-11 | Biogen Idec Ma Inc. | Análogos de esfingosina 1-fosfato de arilo bicíclico |
MX2011005481A (es) | 2008-11-25 | 2011-08-17 | Biogen Idec Inc | Uso de antagonistas de receptor de muerte 6 (drg6) y de p75 para promover la supervivencia de células del sistema nervioso. |
WO2010063352A1 (fr) | 2008-12-01 | 2010-06-10 | Merck Patent Gmbh | Pyrido[4,3-d]pyrimidines 2,5-diamino-substituées en tant qu'inhibiteurs d'autotaxine contre le cancer |
US8455499B2 (en) | 2008-12-11 | 2013-06-04 | Amira Pharmaceuticals, Inc. | Alkyne antagonists of lysophosphatidic acid receptors |
GB2466121B (en) | 2008-12-15 | 2010-12-08 | Amira Pharmaceuticals Inc | Antagonists of lysophosphatidic acid receptors |
JP5591318B2 (ja) | 2009-04-02 | 2014-09-17 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | オートタキシン阻害剤としてのピペリジンおよびピペラジン誘導体 |
US8841324B2 (en) | 2009-04-02 | 2014-09-23 | Merck Patent Gmbh | Heterocyclic compounds as autotaxin inhibitors |
WO2010112124A1 (fr) | 2009-04-02 | 2010-10-07 | Merck Patent Gmbh | Inhibiteurs de l'autotaxine |
GB2470833B (en) | 2009-06-03 | 2011-06-01 | Amira Pharmaceuticals Inc | Polycyclic antagonists of lysophosphatidic acid receptors |
DE102009033392A1 (de) | 2009-07-16 | 2011-01-20 | Merck Patent Gmbh | Heterocyclische Verbindungen als Autotaxin-Inhibitoren II |
EP2462128B1 (fr) | 2009-08-04 | 2016-09-21 | Amira Pharmaceuticals, Inc. | Composés en tant qu'antagonistes du récepteur de l'acide lysophosphatidique |
UA107360C2 (en) | 2009-08-05 | 2014-12-25 | Biogen Idec Inc | Bicyclic aryl sphingosine 1-phosphate analogs |
GB2474120B (en) | 2009-10-01 | 2011-12-21 | Amira Pharmaceuticals Inc | Compounds as Lysophosphatidic acid receptor antagonists |
GB2474748B (en) | 2009-10-01 | 2011-10-12 | Amira Pharmaceuticals Inc | Polycyclic compounds as lysophosphatidic acid receptor antagonists |
AR079022A1 (es) | 2009-11-02 | 2011-12-21 | Sanofi Aventis | Derivados de acido carboxilico ciclico sustituidos con acilamino, su uso como productos farmaceuticos, composicion farmaceutica y metodo de preparacion |
RU2559540C2 (ru) | 2009-12-16 | 2015-08-10 | Ново Нордиск А/С | Дважды ацилированные производные glp-1 |
ES2562183T3 (es) | 2010-03-26 | 2016-03-02 | Merck Patent Gmbh | Benzonaftiridinaminas como inhibidores de la autotaxina |
WO2011133862A1 (fr) | 2010-04-23 | 2011-10-27 | Oregon Health And Science University | Procédés et compositions pour stimuler la myélinisation |
EP2569924A4 (fr) | 2010-05-13 | 2014-12-24 | Nokia Corp | Procédé et appareil pour détection et fusion de contexte |
ES2593256T3 (es) * | 2010-05-21 | 2016-12-07 | Infinity Pharmaceuticals, Inc. | Compuestos químicos, composiciones y métodos para las modulaciones de cinasas |
WO2011159550A2 (fr) | 2010-06-14 | 2011-12-22 | Amidra Pharmaceuticals, Inc. | Antagoniste du récepteur de l'acide lysophosphatidique et ses utilisations |
WO2011159635A1 (fr) | 2010-06-15 | 2011-12-22 | Amira Pharmaceuticals, Inc. | Antagoniste de récepteur d'acide lysophosphatidique pour le traitement d'affections dermiques |
BR112012031580A2 (pt) | 2010-07-06 | 2016-11-08 | Ono Pharmaceutical Co | derivado de tetra-hidrocarbolina |
US9000025B2 (en) | 2010-08-20 | 2015-04-07 | Amira Pharmaceuticals, Inc. | Autotaxin inhibitors and uses thereof |
US8859775B2 (en) | 2010-09-02 | 2014-10-14 | Merck Patent Gmbh | Pyrazolopyridinone derivatives as LPA receptor antagonists |
CN103209711B (zh) | 2010-11-09 | 2016-04-13 | 诺沃—诺迪斯克有限公司 | 双-酰化的glp-1衍生物 |
BR112013014019A2 (pt) | 2010-12-07 | 2016-09-13 | Amira Pharmaceuticals Inc | antagonistas do receptor do ácido lisofosfatídico e seus usos |
HUE040397T2 (hu) | 2010-12-07 | 2019-03-28 | Amira Pharmaceuticals Inc | Policiklikus LPA1-antagonista és felhasználása |
KR20140038358A (ko) | 2011-01-11 | 2014-03-28 | 페이트 세러퓨틱스, 인코포레이티드 | 신규의 Wnt 조성물 및 이러한 조성물의 치료학적 용도 |
MX342145B (es) | 2011-02-07 | 2016-09-15 | Biogen Ma Inc | Agentes moduladores de esfingosina 1-fosfato (s1p). |
JP6022538B2 (ja) | 2011-04-12 | 2016-11-09 | ノヴォ ノルディスク アー/エス | 二重アシル化されたglp−1誘導体 |
EP2714680B1 (fr) | 2011-05-27 | 2015-11-25 | Amira Pharmaceuticals, Inc. | Inhibiteurs de l'autotaxine hétérocycliques et leurs utilisations |
GB2494679A (en) | 2011-09-15 | 2013-03-20 | Univ Jw Goethe Frankfurt Main | Treatment of neuropathic pain and nerve injury by Nox4 inhibition |
US9873722B2 (en) | 2011-09-16 | 2018-01-23 | Fate Therapeutics, Inc. | Wnt compositions and therapeutic uses of such compositions |
EP2763976B1 (fr) | 2011-10-05 | 2016-05-18 | Merck Sharp & Dohme Corp. | Inhibiteurs de tyrosine kinase de la rate (syk) contenant un 2-pyridyl carboxamide |
WO2013054185A1 (fr) | 2011-10-13 | 2013-04-18 | Pfizer, Inc. | Dérivés de pyrimidine et de pyridine utiles en thérapie |
JP2014528486A (ja) | 2011-10-13 | 2014-10-27 | ケース ウエスタン リザーブ ユニバーシティ | Rxrアゴニスト化合物および方法 |
CA2853258A1 (fr) | 2011-10-24 | 2013-05-02 | Abbvie Inc. | Agents de liaison immunologique diriges contre la sclerostine |
ES2648901T3 (es) | 2011-10-28 | 2018-01-08 | Inhibitaxin Limited | Derivados de piridazina útiles en terapia |
WO2013070879A1 (fr) | 2011-11-10 | 2013-05-16 | Bristol-Myers Squibb Company | Méthodes de traitement de lésion de la moelle épinière par des antagonistes du récepteur du lpa |
EA201491060A1 (ru) | 2011-11-28 | 2014-09-30 | Новартис Аг | Новые производные трифторметилоксадиазола и их применение для лечения заболевания |
US10653650B2 (en) | 2011-12-13 | 2020-05-19 | Io Therapeutics, Inc. | Treatment of diseases by concurrently eliciting remyelination effects and immunomodulatory effects using selective RXR agonists |
PL3130347T3 (pl) | 2011-12-30 | 2020-04-30 | Halozyme, Inc. | Warianty polipeptydu ph20, ich formulacje i zastosowania |
CA2873623C (fr) | 2012-05-14 | 2021-11-09 | Biogen Idec Ma Inc. | Antagonistes de lingo-2 pour le traitement d'affections impliquant des neurones moteurs |
HUE030526T2 (en) | 2012-06-13 | 2017-05-29 | Hoffmann La Roche | New diazaspirocycloalkane and azaspirocycloalkane |
JP6391571B2 (ja) | 2012-07-27 | 2018-09-19 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Atx調節剤 |
US9550798B2 (en) | 2012-07-27 | 2017-01-24 | Biogen Ma Inc. | Compounds that are S1P modulating agents and/or ATX modulating agents |
WO2014018887A1 (fr) | 2012-07-27 | 2014-01-30 | Biogen Idec Ma Inc. | Agents de modulation d'atx |
US9499485B2 (en) | 2012-08-06 | 2016-11-22 | Biogen Ma Inc. | Compounds that are S1P modulating agents and/or ATX modulating agents |
EP2879674B1 (fr) | 2012-08-06 | 2017-11-22 | Biogen MA Inc. | Composés étant des agents de modulation de s1p et/ou des agents de modulation d'atx |
BR112015004111A2 (pt) | 2012-09-25 | 2017-07-04 | Hoffmann La Roche | novos derivados bicíclicos |
EP2906240A2 (fr) | 2012-10-09 | 2015-08-19 | Biogen MA Inc. | Polythérapies et leurs utilisations pour le traitement de troubles de la démyélinisation |
EP2914591B1 (fr) | 2012-11-03 | 2017-10-11 | Boehringer Ingelheim International GmbH | Inhibiteurs de cytomégalovirus |
WO2014081756A1 (fr) | 2012-11-20 | 2014-05-30 | Biogen Idec Ma Inc. | Agents de modulation de s1p et/ou atx |
US9850206B2 (en) | 2012-11-20 | 2017-12-26 | Biogen Ma Inc. | S1P and/or ATX modulating agents |
MX2015007936A (es) | 2012-12-19 | 2016-03-11 | Novartis Ag | Inhibidores de autotaxina. |
WO2014106104A1 (fr) | 2012-12-28 | 2014-07-03 | Biogen Idec Ma Inc. | Utilisation d'antagonistes dr6 pour atténuer une affection des motoneurones |
TWI499591B (zh) | 2013-01-11 | 2015-09-11 | Lilly Co Eli | 雙環嘧啶化合物 |
US9879075B2 (en) | 2013-02-06 | 2018-01-30 | Yokohama City University and Chiome Bioscience Inc. | Anti-semaphorin 3A antibody and treatment of Alzheimer's disease and inflammatory immune diseases using same |
WO2014133112A1 (fr) | 2013-03-01 | 2014-09-04 | 国立大学法人東京大学 | Dérivé imidazopyrimidinone substitué en position 8 présentant une activité inhibitrice de l'autotaxine |
AR095079A1 (es) | 2013-03-12 | 2015-09-16 | Hoffmann La Roche | Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo |
TW201520219A (zh) | 2013-03-12 | 2015-06-01 | Lilly Co Eli | 咪唑並吡啶化合物 |
PT3269716T (pt) | 2013-03-14 | 2020-10-09 | Galapagos Nv | Novos compostos e suas composições farmacêuticas para o tratamento de doenças inflamatórias |
TW201446768A (zh) | 2013-03-15 | 2014-12-16 | Biogen Idec Inc | S1p及/或atx調節劑 |
AU2014247953A1 (en) | 2013-04-05 | 2015-11-12 | Mitobridge, Inc. | PPAR agonists |
TW201500356A (zh) | 2013-04-12 | 2015-01-01 | Lilly Co Eli | 二氫吡啶并嘧啶化合物 |
WO2014197818A2 (fr) | 2013-06-07 | 2014-12-11 | The General Hospital Corporation | Activateurs de petites molécules de la voie nrf2 |
JP6435323B2 (ja) | 2013-06-19 | 2018-12-05 | ガラパゴス・ナムローゼ・フェンノートシャップGalapagos N.V. | 炎症性障害の治療のための新規化合物及びその医薬組成物 |
JP6475233B2 (ja) | 2013-06-20 | 2019-02-27 | ノヴォ ノルディスク アー/エス | Glp−1誘導体及びその使用 |
WO2015001352A1 (fr) | 2013-07-03 | 2015-01-08 | The University Court Of The University Of Edinburgh | Nouvelle thérapie régénérative |
AU2014286234A1 (en) | 2013-07-04 | 2015-12-17 | Novo Nordisk A/S | Derivatives of GLP-1 like peptides, and uses thereof |
KR20160033726A (ko) | 2013-07-18 | 2016-03-28 | 노파르티스 아게 | 헤테로방향족 고리-벤질-아미드-사이클 코어를 포함하는 오토탁신 억제제 |
WO2015008229A1 (fr) | 2013-07-18 | 2015-01-22 | Novartis Ag | Inhibiteurs de l'autotaxine |
US10285976B2 (en) | 2013-08-12 | 2019-05-14 | The Board Of Trustees Of The Leland Stanford Junior University | 4-methylumbelliferone treatment for immune modulation |
JP2016530210A (ja) | 2013-09-17 | 2016-09-29 | ファーマケア,インク. | ヘテロ環式ビニルオートタキシン阻害剤化合物 |
EP3046905A4 (fr) | 2013-09-17 | 2017-03-22 | Pharmakea Inc. | Composés vinyliques inhibiteurs de l'autotaxine |
EP3049405A4 (fr) | 2013-09-26 | 2017-03-08 | Pharmakea Inc. | Composés inhibiteurs de l'autotaxine |
US9783531B2 (en) | 2013-12-20 | 2017-10-10 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
EP3302465A1 (fr) * | 2015-06-05 | 2018-04-11 | Vertex Pharmaceuticals Incorporated | Triazoles pour le traitement de maladies liées à la démyélinisation |
-
2016
- 2016-06-03 EP EP16738576.4A patent/EP3302465A1/fr not_active Withdrawn
- 2016-06-03 AU AU2016270373A patent/AU2016270373A1/en not_active Abandoned
- 2016-06-03 CA CA2988306A patent/CA2988306A1/fr not_active Abandoned
- 2016-06-03 WO PCT/US2016/035847 patent/WO2016197009A1/fr active Application Filing
- 2016-06-03 US US15/173,177 patent/US10118904B2/en active Active
- 2016-06-04 TW TW105117774A patent/TW201708195A/zh unknown
- 2016-06-06 UY UY0001036713A patent/UY36713A/es not_active Application Discontinuation
-
2018
- 2018-09-12 HK HK18111726.8A patent/HK1252425A1/zh unknown
- 2018-10-17 US US16/162,835 patent/US10766869B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
WO2016197009A1 (fr) | 2016-12-08 |
US10118904B2 (en) | 2018-11-06 |
HK1252425A1 (zh) | 2019-05-24 |
EP3302465A1 (fr) | 2018-04-11 |
AU2016270373A1 (en) | 2018-01-04 |
TW201708195A (zh) | 2017-03-01 |
US10766869B2 (en) | 2020-09-08 |
US20190185436A1 (en) | 2019-06-20 |
US20160355488A1 (en) | 2016-12-08 |
UY36713A (es) | 2017-01-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2988306A1 (fr) | Triazoles pour le traitement de maladies liees a la demyelinisation | |
KR102085121B1 (ko) | 이미다조[1,2-b]피리다진계 화합물, 그를 포함하는 조성물 및 그의 용도 | |
CA3192601A1 (fr) | Composes en tant qu'agonistes de glp-1r | |
CA3161278A1 (fr) | Inhibiteurs de sos1 | |
IL308983A (en) | Pyridazines as PAR7 inhibitors | |
CA3139708A1 (fr) | Phenylaminopyrimidine amides inhibiteurs d'autophagie et leurs procedes d'utilisation | |
EP2953940B1 (fr) | Carboxylates de pipéridin-1-yle et d'azépin-1-yle à titre d'agonistes du récepteur muscarinique m4 | |
EP2367598B1 (fr) | Inhibiteurs de diacylglycérol acyltransférase | |
CA2938294C (fr) | Composes de [1,2,4]triazolo[1,5-a]pyrimidin-7-yle substitues utilisables en tant qu'inhibiteurs de pde2 | |
KR20200074164A (ko) | 무스카린성 아세틸콜린 수용체 m4의 길항제 | |
CA3048376A1 (fr) | Compose inhibiteur de signal bmp | |
CA3001094A1 (fr) | Acides pyrazolo[3,4-b]pyridin-6-carboxyliques substitues et leur utilisation | |
WO2013066729A1 (fr) | Aminopyrimidinones en tant qu'inhibiteurs de kinases associées au récepteur de l'interleukine | |
CN116554151B (zh) | 驱动蛋白kif18a抑制剂及其应用 | |
CA3143489A1 (fr) | Inhibiteurs de l'autophagie a base d'amide d'aminopyrimidine et leurs procedes d'utilisation | |
KR20210068422A (ko) | 심장 근절 억제제 | |
AU2019233183A1 (en) | Phthalazine isoxazole alkoxy derivatives, preparation method thereof, pharmaceutical composition and use thereof | |
WO2017003995A1 (fr) | Composés inhibiteurs de tbk/ikkε et leurs utilisations | |
CA3202355A1 (fr) | Composes pour la degradation de la kinase 2 dependante des cyclines par l'intermediaire d'une voie de l'ubiquitine-proteosome | |
CA3120514A1 (fr) | Urees cycliques | |
CA3079081A1 (fr) | Derives de benzimidazole et leurs utilisations | |
CA3234517A1 (fr) | Compose tetracyclique contenant de l'azote, son procede de preparation et son utilisation medicale | |
KR20200116945A (ko) | 무스카린성 아세틸콜린 수용체 m4의 길항제 | |
CA3228655A1 (fr) | Derive de triazole substitue, son procede de preparation, composition pharmaceutique de celui-ci et utilisation associee | |
JP2022505707A (ja) | 置換インドールおよびインダゾール化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |
Effective date: 20220301 |